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1.
Ivana Tonic Wan-Ni Yu Youngku Park Chia-Chen Chen Nissim Hay 《The Journal of biological chemistry》2010,285(31):23790-23798
Akt is perhaps the most frequently activated oncoprotein in human cancers. Overriding cell cycle checkpoint in combination with the inhibition of apoptosis are two principal requirements for predisposition to cancer. Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis. These activities of Akt cannot be recapitulated by the knockdown of Chk1 alone or by overexpression of Bcl2. Rather the combination of Chk1 knockdown and Bcl2 overexpression is required to recapitulate Akt activities. Akt was shown to directly phosphorylate Chk1. However, we found that Chk1 mutants in the Akt phosphorylation sites behave like wild-type Chk1 in mediating G2 arrest, suggesting that the phosphorylation of Chk1 by Akt is either dispensable for Chk1 activity or insufficient by itself to exert an effect on Chk1 activity. Here we report a new mechanism by which Akt affects G2 cell cycle arrest. We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage. 相似文献
2.
The collective redox activities of transition‐metal (TM) cations and oxygen anions have been shown to increase charge storage capacity in both Li‐rich layered and cation‐disordered rock‐salt cathodes. Repeated cycling involving anionic redox is known to trigger TM migration and phase transformation in layered Li‐ and Mn‐rich (LMR) oxides, however, detailed mechanistic understanding on the recently discovered Li‐rich rock‐salt cathodes is largely missing. The present study systematically investigates the effect of oxygen redox on a Li1.3Nb0.3Mn0.4O2 cathode and demonstrates that performance deterioration is directly correlated to the extent of oxygen redox. It is shown that voltage fade and hysteresis begin only after initiating anionic redox at high voltages, which grows progressively with either deeper oxidation of oxygen at higher potential or extended cycling. In contrast to what is reported on layered LMR oxides, extensive TM reduction is observed but phase transition is not detected in the cycled oxide. A densification/degradation mechanism is proposed accordingly which elucidates how a unique combination of extensive chemical reduction of TM and reduced quality of the Li percolation network in cation‐disordered rock‐salts can lead to performance degradation in these newer cathodes with 3D Li migration pathways. Design strategies to achieve balanced capacity and stability are also discussed. 相似文献
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4.
Toxin–antitoxin (TA) systems are small genetic elements that typically encode a stable toxin and its labile antitoxin. These cognate pairs are abundant in prokaryotes and have been shown to regulate various cellular functions. Vibrio cholerae, a human pathogen that is the causative agent of cholera, harbors at least thirteen TA loci. While functional HigBA, ParDE have been shown to stabilize plasmids and Phd/Doc to mediate cell death in V. cholerae, the function of seven RelBE-family TA systems is not understood. In this study we investigated the function of the RelBE TA systems in V. cholerae physiology and found that six of the seven relBE loci encoded functional toxins in E. coli. Deletion analyses of each relBE locus indicate that RelBE systems are involved in biofilm formation and reactive oxygen species (ROS) resistance. Interestingly, all seven relBE loci are induced under the standard virulence induction conditions and two of the relBE mutants displayed a colonization defect, which was not due to an effect on virulence gene expression. Although further studies are needed to characterize the mechanism of action, our study reveals that RelBE systems are important for V. cholerae physiology. 相似文献
5.
A controlled environment experiment investigated whether thered:far-red (R:FR) ratio of light at the apical bud of the mainstolon could alter plant morphogenesis in clonal cuttings ofwhite clover (Trifolium repens L.) The apical bud included theapical meristem, five to six developing leaf primordia withassociated axillary bud primordia and stipules and the firstemerged folded leaf until development was greater than 0·3on the Carlson scale. Three light regimes were imposed on theapical bud by collimating light from R or FR light-emittingdiodes so that the R:FR ratio of light incident at the apicalbud was set at 0·25, 1·6 or 2·1, withoutsignificantly altering photosynthetically active radiation.The effect of these light regimes on white clover seedling growthwas also tested. At a low R:FR ratio seedling hypocotyl and cotyledon lengthswere significantly longer. However, with the cuttings, the lighttreatments did not alter node appearance rate or internode lengthof the main stolon, petiole length, area of leaves or totalshoot dry matter. There was one significant photomorphogeneticresponse in the cuttings, a delay of 0·5 of a phyllochronin the appearance of branches from axillary buds in the lowR:FR ratio treatment relative to the other treatments. Wherebranch appearance was delayed plants had fewer branches. Thisdifference could be ascribed solely to a delay in branch appearanceas there were no significant treatment effects on either theinitiation of axillary bud primordia within the apical bud,the probability of branching or on the rate of growth of branchesafter appearance. Because treatment of the apical bud inducedonly one of the many previously observed responses of whiteclover to a decrease in the R:FR ratio of light, we concludethat other plant organs must also sense the quality of incidentlight.Copyright 1994, 1999 Academic Press White clover, Trifolium repens, apical bud, light quality, red:far-red ratio, light-emitting diode, branching, axillary buds, photomorphogenesis 相似文献
6.
A three-dimensional investigation of temporomandibular joint loading 总被引:15,自引:0,他引:15
A mathematical model of the muscle groups applied to the human mandible is developed to study the forces developed on the condyles during maximum unilateral occlusion. The results show that the reaction forces are in approximately a 2:1 ratio with the balancing side condyle carrying the greater load. Furthermore, the direction in which these condylar reactions occur is presented. 相似文献
7.
Evidence for a secretory form of the cellular prion protein 总被引:8,自引:0,他引:8
The biogenesis of hamster brain prion protein (PrP) has been studied by expression of RNA transcribed from a full-length PrP cDNA in Xenopus oocytes and cell-free systems. Earlier studies in the wheat germ cell-free system showed that one form of PrP is a transmembrane protein that spans the bilayer at least twice [Hay, B., Barry, R. A., Lieberburg, I., Prusiner, S. B., & Lingappa, V. R. (1987) Mol. Cell. Biol. 7, 914-920]. We now report that PrP can also exist as a secreted protein. SP6 PrP RNA microinjected into Xenopus oocytes produced two forms of PrP: one that remained in the cell and another that was secreted into the medium. Cell-free translation studies in rabbit reticulocyte lysates supplemented with microsomal membranes gave similar results: while one form of PrP was found as an integral membrane protein spanning the membrane at least twice, another form of PrP was found to be completely translocated to the microsomal membrane vesicle lumen. Both the membrane and secretory forms of PrP appear to be generated from the same pool of nascent chains. The mechanism governing the alternative fates of nascent PrP remains to be elucidated but may have significance for understanding the pathogenesis of scrapie and other prion diseases. 相似文献
8.
A sensitive gel retention assay has been utilized to detect proteins from uninfected Hela nuclei which interact with the adenovirus type 2 enhancer. This assay has been employed to monitor fractionation of nuclear extracts. Three enhancer binding factors were resolved by chromatography on DEAE-Sepharose and one of the factors was further purified by chromatography on heparin-Sepharose. DNase protection experiments have shown that the heparin-Sepharose fraction contains a factor which binds predominantly to the conserved sequence GTGGAAATTT present at position 160 in the adenovirus type 2 genome and found in many viral and cellular enhancers. Protection of this sequence from DNase I digestion was abolished by competition with a synthetic duplex oligonucleotide spanning bases 144-181. This region corresponds to the sequence defined by Hen et al. as possessing enhancer function. Competition experiments indicated that the enhancer binding factor also bound, albeit with reduced affinity, to multiple sites in the Ela upstream region located between positions 192 and 353. Within the sequences which compete are regions with homology to the high affinity site at position 160. The enhancer binding factor also binds with high affinity to sequences within the SV40 enhancer demonstrating that this factor interacts with sequences common to both the adenovirus and SV40 enhancers. 相似文献
9.
The action of the beta-agonist clenbuterol on protein metabolism in innervated and denervated phasic muscles. 总被引:3,自引:0,他引:3
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1. Clenbuterol treatment in innervated and denervated phasic extensor digitorum longus, plantaris and gastrocnemius muscles from rats caused a significant increase in RNA and protein contents in all muscles except denervated extensor digitorum longus. 2. All muscles showed an increase in the fractional rate of protein synthesis (Ks) with clenbuterol, but the temporal response varied. 3. The data suggest that the effect of clenbuterol on protein metabolism in innervated muscles is muscle-type specific, and demonstrate the homology of response for denervated muscles. 相似文献
10.
Medial edge epithelium transforms to mesenchyme after embryonic palatal shelves fuse 总被引:8,自引:0,他引:8
The disappearance of palatal medial edge epithelium (MEE) after fusion of secondary palatal shelves is often cited as a classical example of embryonic remodeling by programmed cell death. We reinvestigated this phenomenon in 16-day rat embryos, using light and electron microscopy. We confirm reports that the periderm of the two-layered MEE begins to slough after shelves assume horizontal positions. In vitro, peridermal cells are not able to slough and are trapped during the adhesion process. In vivo, however, surface cells shed before the shelves in the anterior palate adhere, allowing junctions to form between opposing basal epithelial cells. Midline seams so formed consist of two layers of basal cells, all of which appear healthy. Even though its cells are dividing, growth of the seam fails to keep pace with palatal growth and it thins to one layer of cells, and then breaks up into small islands. The basal lamina disappears and elongating MEE cells extend filopodia into adjacent connective tissue. Electron micrographs reveal transitional steps in loss of epithelial characteristics and gain of fibroblast-like features by transforming MEE cells. One such feature, observed with the aid of immunofluorescence, is the turn of the mesenchymal cytoskeletal protein, vimentin. No cell death or macrophages are observed after adhesion and thinning over most of the palate. These data indicate that MEE is an ectoderm that retains the ability to transform into mesenchymal cells. Epithelial-mesenchymal transformation may be expressed in other embryonic remodelings (R.L. Trelstad, A. Hayashi, K. Hayashi, and P.K. Donahue, 1982, Dev. Biol. 92, 27), resulting in heretofore unsuspected conservation of embryonic cell populations. 相似文献